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The Mk 19 appears in Call of Duty 4: Modern Warfare mounted on the Sea Knight the player travels in throughout the level "Shock and Awe". It cannot be moved from its position, but it has a wide angle of fire. When fired continuously, the Mk 19 quickly overheats and takes several seconds to be ready to fire again. A bar on the HUD can be used to monitor how close the Mk 19 is to overheating. An unusable Mk 19 can also be seen in the armory in the level "F.N.G."

The Mk 19 is used in "Shock and Awe" as a powerful, general purpose weapon. Its high power, blast radius and decent rate of fire make it effective against infantry, vehicles and structures alike. However, the movement of the helicopter can sometimes make firing at moving and partially protected targets difficult.

Also, unusable Mk 19s are found in mission Death From Above, mounted on friendly Sea Knights at the end of the level. They can be easily seen when using 25mm turret or going in noclip mode. This also indicates that the Sea Knights used in this mission and in mission Shock and Ave have same models.